The incidence of malignant melanoma of the skin the most serious form of skin cancer is increasing faster than that of any other cancer in the United States, and this rising incidence is expected to continue for at least the next 20 years. The prognosis for patients with melanoma is determined by the histology of the primary tumor and by the presence and extent of metastatic disease. Accurate staging at diagnosis is important to assess the prognosis and to determine best therapeutic strategy. The physical examination of regional lymph nodes is often inaccurate. More definitive information about the status of the regional nodes can be obtained from elective lymph node dissection (ELND), lymphoscintigraphy with sentinel node biopsy (LSNB), or fine needle aspiration. However, there are several major drawbacks of these procedures. Although some sites of metastatic disease may be clinically apparent, imaging must be used to detect unsuspected metastases almost all patients who die from melanoma do so with disseminated disease. Imaging studies are, therefore, an important component of the evaluation of patients with both localized and advanced melanoma. However, current imaging techniques including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and ultrasound imaging are ineffective in majority of asymptomatic patients with stage I or II disease. Therefore, there is an urgent and definite clinical need for an objective imaging technique that is widely available, is noninvasive and simple to perform, is safe, and can reliably detect and adequately diagnose early lymph node micro-metastases in real- time. The overall goal of our research program is to develop an in-vivo, minimally noninvasive, molecular specific imaging technology magneto-motive ultrasound (MMUS) imaging capable of immediate and accurate assessment of presence and extent of metastatic disease at all stages. In MMUS imaging, the targeted magnetic iron oxide nanoparticles are injected into the tissue and the ultrasound is used both to visualize the tissue and to accurately evaluate the internal tissue motion induced by the externally applied magnetic field. The central theme of the current application is threefold: to design and build a laboratory prototype of the magneto-motive ultrasound imaging system, to develop molecularly sensitive contrast agent for MMUS imaging system, and to initially test the developed MMUS imaging technology in tissue-mimicking phantoms, 3D cell tissue constructs and, finally, small animal cancer model ex-vivo, in vitro and in vivo. The skin is the largest organ in the body, and it is not surprising that cancer of the skin is the most common of all cancers. Melanoma a cancer that begins in skin cells called melanocytes is the most deadly skin cancer, accounting for 79% of skin cancer deaths. Melanoma is currently the sixth most common cancer in American men and the seventh most common in American women. The median age at diagnosis is between 45 and 55, although 25% of cases occur in individuals before age 40. It is the second most common cancer in women between the ages of 20 and 35, and the leading cause of cancer death in women ages 25 to 30. The overall goal of our research program is to develop an advanced, noninvasive (or minimally invasive), real- time imaging technique magneto-motive ultrasound (MMUS) imaging to assess sentinel lymph node metastases thus identifying the best therapeutic intervention including immediate therapy if necessary.